tbuckley/cabot-search huggingface dataset:
CDC6 is a prognostic biomarker and correlated with immune infiltrates in glioma
Authors: Feng Wang, Fen Zhao, Li Zhang, Lai Xiong, Qing Mao, Yanhui Liu, Xiaoguang Qiu, Xiang Wang, Lin Shui, Xi Chen, Kexing Ren, Pixian Shui, Qiongwen Zhang, Yifei Deng, Weimin Li, Xiaoqi Xie, Dengbin Wu, Tao Li, Jinyi Lang, Lei Liu, Huaying Chen, Jianguo Xu, Sen Bai, Zhiping Li, Qiang Yue, Ni Chen, Bingwen Zhou, Cheng Yi, Yuquan Wei, Yuchuan Fu, Yong Luo, Qiheng Gou, Lunxu Liu, Yuanzhao Liu, Jingbo Kang, Junjie Wang, Dongcun Jing, Fuquan Zhang, Xiaoyan Yang, Xianfeng Li, Tao Jiang, Zongcun Zhang, Yizhi Zhou, Junlin Yi
Journal: Molecular Cancer (2022)

Abstract Background Cell division cycle 6 (CDC6) has been proven to be associated with the initiation and progression of human multiple tumors. However, it’s role in glioma, which is ranked as one of the common primary malignant tumor in the central nervous system and is associated with high morbidity and mortality, is unclear. Methods In this study, we explored CDC6 gene expression level in pan-cancer. Furthermore, we focused on the relationships between CDC6 expression, its prognostic value, potential biological functions, and immune infiltrates in glioma patients. We also performed vitro experiments to assess the effect of CDC6 expression on proliferative, apoptotic, migrant and invasive abilities of glioma cells. Results As a result, CDC6 expression was upregulated in multiple types of cancer, including glioma. Moreover, high expression of CDC6 was significantly associated with age, IDH status, 1p/19q codeletion status, WHO grade and histological type in glioma (all p &lt; 0.05). Meanwhile, high CDC6 expression was associated with poor overall survival (OS) in glioma patients, especially in different clinical subgroups. Furthermore, a univariate Cox analysis showed that high CDC6 expression was correlated with poor OS in glioma patients. Functional enrichment analysis indicated that CDC6 was mainly involved in pathways related to DNA transcription and cytokine activity, and Gene Set Enrichment Analysis (GSEA) revealed that MAPK pathway, P53 pathway and NF-κB pathway in cancer were differentially enriched in glioma patients with high CDC6 expression. Single-sample gene set enrichment analysis (ssGSEA) showed CDC6 expression in glioma was positively correlated with Th2 cells, Macrophages and Eosinophils, and negative correlations with plasmacytoid dendritic cells, CD8 T cells and NK CD56bright cells, suggesting its role in regulating tumor immunity. Finally, CCK8 assay, flow cytometry and transwell assays showed that silencing CDC6 could significantly inhibit proliferation, migration, invasion, and promoted apoptosis of U87 cells and U251 cells ( p &lt; 0.05). Conclusion In conclusion, high CDC6 expression may serve as a promising biomarker for prognosis and correlated with immune infiltrates, presenting to be a potential immune therapy target in glioma.
Disentangling the Causal Effect of Telomere Length in Systemic Lupus Erythematosus Using Genetic Variants as Instruments
Authors: Yiqiang Zhan, Xiaoying Kang
Journal: Arthritis & Rheumatology (2022)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Safety-netting in the consultation
Authors: Peter J Edwards, Paul Silverston, Jane Sprackman, Damian Roland
Journal: BMJ (2022)

### What you need to know Safety-netting has become a widely used term to describe an array of activities both within the consultation and on systems levels. Within the consultation, safety-netting is considered best practice, and often an expected clinical standard, particularly in primary and emergency care.12 The term was first coined by Roger Neighbour in 1987 as an in-consultation tool for managing clinical uncertainty.3 Safety-netting advice has since been defined as: "Information shared with a patient or their carer, designed to help them identify the need to seek further medical help if their condition fails to improve, changes, or if they have concerns about their health."45 This article outlines the principles and evidence base (box 1) of safety-netting and offers an approach to giving effective safety-netting advice. Box 1 ### Is there an evidence base for safety-netting? A literature review in 2019 reported the most common type of safety-netting article was an expert opinion (n=25), followed by qualitative studies (n=12), with no completed randomised controlled trial (RCT).6 An updated realist review in 2022, which produced 15 recommendations to enhance the communication of safety-netting advice, included reference to two randomised trials, but neither had a primary intervention of safety-netting or referred to this term.7 However, there have been multiple RCTs of treating common infections with arms comparing patient information leaflets (which commonly contain safety-netting advice) against no leaflets. In a systematic review of such studies, six of the seven RCT leaflets included safety-netting advice (one was unclear), which demonstrated an overall trend towards … RETURN TO TEXT
Subsets of Idiopathic Inflammatory Myositis Enriched for Contemporaneous Cancer Relative to the General Population
Authors: Christopher A. Mecoli, Tak Igusa, Mengkun Chen, XingYao Wang, Jemima Albayda, Julie J. Paik, Eleni Tiniakou, Brittany Adler, Carrie Richardson, Will Kelly, Sonye Danoff, Andrew L. Mammen, Elizabeth A. Platz, Antony Rosen, Lisa Christopher‐Stine, Livia Casciola‐Rosen, Ami A. Shah
Journal: Arthritis & Rheumatology (2022)

Objective This study investigates cancer risk in idiopathic inflammatory myopathy (IIM) relative to the general population. Methods We conducted a single‐center, retrospective cohort study of IIM patients and malignancy. Myositis‐specific and ‐associated autoantibodies were determined by Euroimmun line blot, enzyme‐linked immunosorbent assay, and immunoprecipitation. We calculated standardized prevalence ratios (SPRs) and adjusted for calendar year, age, sex, race, and ethnicity by comparing observed cancers in IIM patients versus expected cancers in the general population using the Surveillance, Epidemiology, and End Results registry. Results Of 1,172 IIM patients, 203 (17%) patients with a cancer history were studied. Over a median follow‐up of 5.2 years, the observed number of IIM patients diagnosed with cancer was increased 1.43‐fold (SPR 1.43 [95% confidence interval (95% CI) 1.15–1.77]; P = 0.002). Within 3 years of IIM symptom onset, an increased SPR was observed for anti–transcription intermediary factor 1γ (anti‐TIF1γ)–positive patients for ovarian and breast cancer (ovarian SPR 18.39 [95% CI 5.01–47.08], P &lt; 0.001; breast SPR 3.84 [95% CI 1.99–6.71], P &lt; 0.001). As expected, anti‐TIF1γ positivity was associated with a significantly elevated SPR; however, only 55% (36 of 66) of all cancers within 3 years of dermatomyositis onset were observed in anti‐TIF1γ–positive patients. Other myositis‐specific autoantibodies, including anti–Mi‐2, anti–small ubiquitin‐like modifier activating enzyme (SAE), and anti‐nuclear matrix protein 2 (NXP‐2), accounted for 26% (17 of 66) of cancers diagnosed within 3 years of dermatomyositis onset. No cancer association, positive or negative, was observed for patients with antisynthetase, anti–melanoma differentiation–associated protein 5 (anti–MDA‐5), or anti–hydroxymethylglutaryl‐coenzyme A reductase (anti‐HMGCR) antibodies. Conclusion In a tertiary referral center population, anti‐TIF1γ was most strongly associated with breast and ovarian cancer. Patients with antisynthetase, anti–MDA‐5, or anti‐HMGCR antibodies had the same cancer risk as the general population. image
Deep Learning vs Traditional Breast Cancer Risk Models to Support Risk-Based Mammography Screening
Authors: Constance D Lehman, Sarah Mercaldo, Leslie R Lamb, Tari A King, Leif W Ellisen, Michelle Specht, Rulla M Tamimi
Journal: JNCI Journal of the National Cancer Institute (2022)

Deep learning breast cancer risk models demonstrate improved accuracy compared with traditional risk models but have not been prospectively tested. We compared the accuracy of a deep learning risk score derived from the patient's prior mammogram to traditional risk scores to prospectively identify patients with cancer in a cohort due for screening.We collected data on 119 139 bilateral screening mammograms in 57 617 consecutive patients screened at 5 facilities between September 18, 2017, and February 1, 2021. Patient demographics were retrieved from electronic medical records, cancer outcomes determined through regional tumor registry linkage, and comparisons made across risk models using Wilcoxon and Pearson χ2 2-sided tests. Deep learning, Tyrer-Cuzick, and National Cancer Institute Breast Cancer Risk Assessment Tool (NCI BCRAT) risk models were compared with respect to performance metrics and area under the receiver operating characteristic curves.Cancers detected per thousand patients screened were higher in patients at increased risk by the deep learning model (8.6, 95% confidence interval [CI] = 7.9 to 9.4) compared with Tyrer-Cuzick (4.4, 95% CI = 3.9 to 4.9) and NCI BCRAT (3.8, 95% CI = 3.3 to 4.3) models (P &lt; .001). Area under the receiver operating characteristic curves of the deep learning model (0.68, 95% CI = 0.66 to 0.70) was higher compared with Tyrer-Cuzick (0.57, 95% CI = 0.54 to 0.60) and NCI BCRAT (0.57, 95% CI = 0.54 to 0.60) models. Simulated screening of the top 50th percentile risk by the deep learning model captured statistically significantly more patients with cancer compared with Tyrer-Cuzick and NCI BCRAT models (P &lt; .001).A deep learning model to assess breast cancer risk can support feasible and effective risk-based screening and is superior to traditional models to identify patients destined to develop cancer in large screening cohorts.
Engineering H<sub>2</sub>O<sub>2</sub> and O<sub>2</sub> Self‐Supplying Nanoreactor to Conduct Synergistic Chemiexcited Photodynamic and Calcium‐Overloaded Therapy in Orthotopic Hepatic Tumors
Authors: Ying‐Chi Chen, Yu‐Ju Liu, Chin‐Lai Lee, Khang‐Yen Pham, Divinah Manoharan, Suresh Thangudu, Chia‐Hao Su, Chen‐Sheng Yeh
Journal: Advanced Healthcare Materials (2022)

Photodynamic therapy (PDT) is traditionally ineffective for deeply embedded tumors due to the poor penetration depth of the excitation light. Chemiluminescence resonance energy transfer (CRET) has emerged as a promising mode of PDT without external light. To date, related research has frequently used endogenous hydrogen peroxide (H2 O2 ) and oxygen (O2 ) inside the solid tumor microenvironment to trigger CRET-mediated PDT. Unfortunately, this significantly restricts treatment efficacy and the development of further biomedical applications because of the limited amounts of endogenous H2 O2 and O2 . Herein, a nanohybrid (mSiO2 /CaO2 /CPPO/Ce6: mSCCC) nanoparticle (NP) is designed to achieve synergistic CRET-mediated PDT and calcium (Ca2+ )-overload-mediated therapy. The calcium peroxide (CaO2 ) formed inside mesoporous SiO2 (mSC) with the inclusion of the chemiluminescent agent (CPPO) and photosensitizer (Ce6) self-supplies H2 O2 , O2 , and Ca2+ allowing for the subsequent treatments. The Ce6 in mSCCC NPs is excited by chemical energy in situ following the supply of H2 O2 and O2 to produce singlet oxygen (1 O2 ). The nanohybrid NPs are coated with stearic acid to avoid decomposition during blood circulation through contact with aqueous environment. This nanohybrid shows promising performance in the generation of 1 O2 for external light-free PDT and the release of Ca2+ ions for Ca2+ -overloaded therapy against orthotopic hepatocellular carcinoma.
Supranormal Left Ventricular Ejection Fraction, Stroke Volume, and Cardiovascular Risk
Authors: Sonia Shah, Matthew W. Segar, Nitin Kondamudi, Colby Ayers, Alvin Chandra, Susan Matulevicius, Kartik Agusala, Ron Peshock, Suhny Abbara, Erin D. Michos, Mark H. Drazner, Joao A.C. Lima, W.T. Longstreth, Ambarish Pandey
Journal: JACC Heart Failure (2022)
Standardized Definitions for Bioprosthetic Valve Dysfunction Following Aortic or Mitral Valve Replacement
Authors: Philippe Pibarot, Howard C. Herrmann, Changfu Wu, Rebecca T. Hahn, Catherine M. Otto, Amr E. Abbas, John Chambers, Marc R. Dweck, Jonathon A. Leipsic, Matheus Simonato, Toby Rogers, Janarthanan Sathananthan, Mayra Guerrero, Julien Ternacle, Harindra C. Wijeysundera, Lars Sondergaard, Marco Barbanti, Erwan Salaun, Philippe Généreux, Tsuyoshi Kaneko, Uri Landes, David A. Wood, G. Michael Deeb, Stephanie L. Sellers, John Lewis, Mahesh Madhavan, Linda Gillam, Michael Reardon, Sabine Bleiziffer, Patrick T. O’Gara, Josep Rodés-Cabau, Paul A. Grayburn, Patrizio Lancellotti, Vinod H. Thourani, Jeroen J. Bax, Michael J. Mack, Martin B. Leon
Journal: Journal of the American College of Cardiology (2022)

Bioprosthetic valve dysfunction (BVD) and bioprosthetic valve failure (BVF) may be caused by structural or nonstructural valve dysfunction. Both surgical and transcatheter bioprosthetic valves have limited durability because of structural valve deterioration. The main objective of this summary of experts participating in a virtual workshop was to propose standardized definitions for nonstructural and structural BVD and BVF following aortic or mitral biological valve replacement with the goal of facilitating research reporting and implementation of these terms in clinical practice. Definitions of structural BVF, based on valve reintervention or death, underestimate the true incidence of BVF. However, definitions solely based on the presence of high transprosthetic gradient at a given echocardiogram during follow-up overestimate the incidence of structural BVD and BVF. Definitions of aortic or mitral structural BVD must therefore include the confirmation by imaging of permanent structural changes to the leaflets alongside evidence of deterioration in valve hemodynamic function at echocardiography follow-up.
Impact of Peridevice Leak on 5-Year Outcomes After Left Atrial Appendage Closure
Authors: Srinivas R Dukkipati, David R Holmes, Shephal K Doshi, Saibal Kar, Sheldon M Singh, Douglas Gibson, Matthew J Price, Andrea Natale, Moussa Mansour, Horst Sievert, Vicki M Houle, Dominic J Allocco, Vivek Y Reddy
Journal: Journal of the American College of Cardiology (2022)
Transcription factors TCF-1 and GATA3 are key factors for the epigenetic priming of early innate lymphoid progenitors toward distinct cell fates
Authors: Gang Ren, Binbin Lai, Christelle Harly, Songjoon Baek, Yi Ding, Mingzhu Zheng, Yaqiang Cao, Kairong Cui, Yu Yang, Jinfang Zhu, Gordon L. Hager, Avinash Bhandoola, Keji Zhao
Journal: Immunity (2022)
Phosphoproteomics of three exercise modalities identifies canonical signaling and C18ORF25 as an AMPK substrate regulating skeletal muscle function
Authors: Ronnie Blazev, Christian S. Carl, Yaan-Kit Ng, Jeffrey Molendijk, Christian T. Voldstedlund, Yuanyuan Zhao, Di Xiao, Andrew J. Kueh, Paula M. Miotto, Vanessa R. Haynes, Justin P. Hardee, Jin D. Chung, James W. McNamara, Hongwei Qian, Paul Gregorevic, Jonathan S. Oakhill, Marco J. Herold, Thomas E. Jensen, Leszek Lisowski, Gordon S. Lynch, Garron T. Dodd, Matthew J. Watt, Pengyi Yang, Bente Kiens, Erik A. Richter, Benjamin L. Parker
Journal: Cell Metabolism (2022)
Molecular signatures underlying neurofibrillary tangle susceptibility in Alzheimer’s disease
Authors: Marcos Otero-Garcia, Sameehan U. Mahajani, Debia Wakhloo, Weijing Tang, Yue-Qiang Xue, Samuel Morabito, Jie Pan, Jane Oberhauser, Angela E. Madira, Tamara Shakouri, Yongning Deng, Thomas Allison, Zihuai He, William E. Lowry, Riki Kawaguchi, Vivek Swarup, Inma Cobos
Journal: Neuron (2022)
Large-scale manipulation of promoter DNA methylation reveals context-specific transcriptional responses and stability
Authors: Alex de Mendoza, Trung Viet Nguyen, Ethan Ford, Daniel Poppe, Sam Buckberry, Jahnvi Pflueger, Matthew R. Grimmer, Sabine Stolzenburg, Ozren Bogdanovic, Alicia Oshlack, Peggy J. Farnham, Pilar Blancafort, Ryan Lister
Journal: Genome biology (2022)

Abstract Background Cytosine DNA methylation is widely described as a transcriptional repressive mark with the capacity to silence promoters. Epigenome engineering techniques enable direct testing of the effect of induced DNA methylation on endogenous promoters; however, the downstream effects have not yet been comprehensively assessed. Results Here, we simultaneously induce methylation at thousands of promoters in human cells using an engineered zinc finger-DNMT3A fusion protein, enabling us to test the effect of forced DNA methylation upon transcription, chromatin accessibility, histone modifications, and DNA methylation persistence after the removal of the fusion protein. We find that transcriptional responses to DNA methylation are highly context-specific, including lack of repression, as well as cases of increased gene expression, which appears to be driven by the eviction of methyl-sensitive transcriptional repressors. Furthermore, we find that some regulatory networks can override DNA methylation and that promoter methylation can cause alternative promoter usage. DNA methylation deposited at promoter and distal regulatory regions is rapidly erased after removal of the zinc finger-DNMT3A fusion protein, in a process combining passive and TET-mediated demethylation. Finally, we demonstrate that induced DNA methylation can exist simultaneously on promoter nucleosomes that possess the active histone modification H3K4me3, or DNA bound by the initiated form of RNA polymerase II. Conclusions These findings have important implications for epigenome engineering and demonstrate that the response of promoters to DNA methylation is more complex than previously appreciated.
Perioperative Fully Closed-Loop Insulin Delivery in Patients Undergoing Elective Surgery: An Open-Label, Randomized Controlled Trial
Authors: David Herzig, Simon Suhner, Jonathan Roos, Daniel Schürch, Luca Cecchini, Christos T. Nakas, Salome Weiss, Alexander Kadner, Gregor J. Kocher, Dominik P. Guensch, Malgorzata E. Wilinska, Andreas Raabe, Klaus A. Siebenrock, Guido Beldi, Beat Gloor, Roman Hovorka, Andreas P. Vogt, Lia Bally
Journal: Diabetes Care (2022)

OBJECTIVE Perioperative management of glucose levels remains challenging. We aimed to assess whether fully closed-loop subcutaneous insulin delivery would improve glycemic control compared with standard insulin therapy in insulin-requiring patients undergoing elective surgery. RESEARCH DESIGN AND METHODS We performed a single-center, open-label, randomized controlled trial. Patients with diabetes (other than type 1) undergoing elective surgery were recruited from various surgical units and randomly assigned using a minimization schedule (stratified by HbA1c and daily insulin dose) to fully closed-loop insulin delivery with fast-acting insulin aspart (closed-loop group) or standard insulin therapy according to local clinical practice (control group). Study treatment was administered from hospital admission to discharge (for a maximum of 20 days). The primary end point was the proportion of time with sensor glucose in the target range (5.6–10.0 mmol/L). RESULTS Forty-five patients were enrolled and assigned to the closed-loop (n = 23) or the control (n = 22) group. One patient (closed-loop group) withdrew from the study before surgery and was not analyzed. Participants underwent abdominal (57%), vascular (23%), orthopedic (9%), neuro (9%), or thoracic (2%) surgery. The mean proportion of time that sensor glucose was in the target range was 76.7 ± 10.1% in the closed-loop and 54.7 ± 20.8% in the control group (mean difference 22.0 percentage points [95% CI 11.9; 32.0%]; P &amp;lt; 0.001). No episodes of severe hypoglycemia (&amp;lt;3.0 mmol/L) or hyperglycemia with ketonemia or any study-related adverse events occurred in either group. CONCLUSIONS In the context of mixed elective surgery, the use of fully closed-loop subcutaneous insulin delivery improves glucose control without a higher risk of hypoglycemia.
Obesity and heart failure with preserved ejection fraction: new insights and pathophysiological targets
Authors: Barry A Borlaug, Michael D Jensen, Dalane W Kitzman, Carolyn S P Lam, Masaru Obokata, Oliver J Rider
Journal: Cardiovascular Research (2022)

Abstract Obesity and heart failure with preserved ejection fraction (HFpEF) represent two intermingling epidemics driving perhaps the greatest unmet health problem in cardiovascular medicine in the 21st century. Many patients with HFpEF are either overweight or obese, and recent data have shown that increased body fat and its attendant metabolic sequelae have widespread, protean effects systemically and on the cardiovascular system leading to symptomatic HFpEF. The paucity of effective therapies in HFpEF underscores the importance of understanding the distinct pathophysiological mechanisms of obese HFpEF to develop novel therapies. In this review, we summarize the current understanding of the cardiovascular and non-cardiovascular features of the obese phenotype of HFpEF, how increased adiposity might pathophysiologically contribute to the phenotype, and how these processes might be targeted therapeutically.
Abstract 9231: The Association of Calcium Supplementation and Incident Cardiovascular Events: Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Subhashish Agarwal, Jennifer A Nettleton, Ian de Boer, Joachim H Ix, David Siscovick, John Eng, Diane Bild, Gregory L Burke, David M Herrington
Journal: Circulation (2012)

Introduction: Some reports indicate that calcium supplements are associated with adverse cardiovascular (CVD) events in post-menopausal women. We investigated the association between calcium supplements and CVD events in a multi-ethnic cohort. Methods: We studied 6,237 participants (2472 Caucasian, 790 Chinese, 1615 African-American, and 1360 Hispanic) in the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort study of adults, ages 45-84, free of clinical CVD who had data on dietary calcium intake, calcium supplements and covariates. Cox proportional hazard models were used to study the association between daily calcium supplements (none [reference], 1-500 mg, 500-1000 mg, and &gt;1000 mg) and 6.1 year incident CVD events after adjusting for age, race, sex, education level, household income, site, total and HDL cholesterol, dietary calcium intake, lipid medication use, systolic blood pressure, anti-hypertensive medications, diabetes status, body mass index (BMI), estimated glomerular filtration rate (eGFR), physical activity, and smoking. Results: Calcium supplements were taken by 2,870 MESA participants. There were 357 CVD events over 6.1 years of follow up. The cumulative 6.1 year CVD event rate for calcium supplement was 5.5% versus 6.4% for non-users. Adjusted hazard ratio (HR, 95% CI) for incident CVD for any calcium supplementation versus none was 0.92 (0.74-1.14). HR's (95%CI) were: Calcium 1-500: 0.84 (0.64-1.08); Calcium 500-1000: 0.89 (0.58-1.32); and Calcium 1000 mg: 1.21 (0.84-1.70). In a similar separate analysis of postmenopausal women (n=2,703), calcium supplement, as in above-mentioned categories, was not associated with incident CVD events. Additionally, no significant interaction was noted between calcium supplements and incident CVD events by race or chronic kidney disease (CKD=eGFR ≤ 60 ml/min/1.73 m 2 ), (calcium x race, p=0.3; calcium x CKD, p=0.9). Conclusion: In this multi-ethnic observational cohort calcium supplementation was not associated with incident CVD events in either men or women including postmenopausal women.